Nrf2-mediated antioxidant response by ethanolic extract ofSida cordifoliaprovides protection against alcohol-induced oxidative stress in liver by upregulation of glutathione metabolism

Abstract

Objective The study aimed to evaluate the antioxidant property of ethanolic extract of Sida cordifolia (SAE) on alcohol-induced oxidative stress and to elucidate its mechanism of action. Methods Male albino rats of the Sprague-Dawley strain were grouped into four: (1) control, (2) alcohol (4 g/kg body weight), (3) SAE (50 mg/100 g body weight), and (4) alcohol (4 g/kg body weight) + SAE (50 mg/100 g body weight). Alcohol and SAE were given orally each day by gastric intubation. The duration of treatment was 90 days. Results The activities of toxicity markers in liver and serum increased significantly in alcohol-treated rats and to a lesser extent in the group administered SAE + alcohol. The activity of alcohol dehydrogenase and the reactive oxygen species level were increased significantly in alcohol-treated rats but attenuated in the SAE co-administered group. Oxidative stress was increased in alcohol-treated rats as evidenced by the lowered activities of antioxidant enzymes, decreased level of reduced glutathione (GSH), increased lipid peroxidation products, and decreased expression of γ-glutamyl cysteine synthase in liver. The co-administration of SAE with alcohol almost reversed these changes. The activity of glutathione-S-transferase and translocation of Nrf2 from cytosol to nucleus in the liver was increased in both the alcohol and alcohol + SAE groups, but the maximum changes were observed in the latter group. Discussion The SAE most likely elicits its antioxidant potential by reducing oxidative stress, enhancing the translocation of Nrf2 to nucleus and thereby regulating glutathione metabolism, leading to enhanced GSH content.

Protective effects of curcumin on acute gentamicin-induced nephrotoxicity in rats

“…Nrf2/HO-1 activation also exerts renoprotective role in alcohol-induced oxidative stress in liver (Rejitha et al 2014) and cerebral ischemic injury (Zhao et al 2014). At cellular and molecular levels, recent studies have demonstrated that CUR attenuates ROS generation and activates signaling pathways that involve the release of Nrf2, promoting transcription of genes that induce the expression of antioxidant system (Shehzad and Lee 2013).…”

Enzyme-Treated Zizania latifolia Extract Protects against Alcohol-Induced Liver Injury by Regulating the NRF2 Pathway

“…Recently, studies inducing the expression of antioxidant genes through the activation of Nrf2 using naturally occurring or artificially synthesized small molecules have been conducted [45][46][47]. It was found that Nrf2 has a protective effect against alcohol-induced acute liver injury and carbon tetrachloride-induced liver injury, and that the expression of Nrf2 transcription factor is increased due to oxidative stress by CYP2E1 in hepatocytes [48,49]. Under oxidative stress, oxidative modification of Keap1 allows Nrf2 to release from Keap1, and then Nrf2 translocates into the nucleus.…”

Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin

“…In order to explore the mechanism, the influence of VC-IV on Nrf2/ARE pathway was examined in this study. Under homeostatic conditions, Nrf2 is present in the cytoplasm attaching to a cytosolic protein Keap1, which functions as a suppressor of Nrf2 by retaining it in cytosol and enhancing its proteasomal degradation via ubiquitination [33,34]. But upon activation, Nrf2 acts as a key transcriptional factor that triggers the ARE pathway, and in turn regulates the expression of several antioxidant and phase II detoxifying enzymes [33].…”

“…Under homeostatic conditions, Nrf2 is present in the cytoplasm attaching to a cytosolic protein Keap1, which functions as a suppressor of Nrf2 by retaining it in cytosol and enhancing its proteasomal degradation via ubiquitination [33,34]. But upon activation, Nrf2 acts as a key transcriptional factor that triggers the ARE pathway, and in turn regulates the expression of several antioxidant and phase II detoxifying enzymes [33]. Consistent with the results from other studies, the results of the present study showed that HO1 and NQO1 expression in the CDDP-treated group was lower than those of vehicle-treated mice.…”